Ovulation-inducing factor: implications for mammalian fertility

排卵是所有哺乳动物生殖过程中的基本事件。排卵失败或排卵不及时对生育有着深远的影响。来自申请人实验室的令人兴奋的数据现在为引发排卵级联的因素提供了新的线索。结果证明精浆中存在一种新的排卵诱导因子(OIF)，并为OIF作为控制排卵时间的机制在哺乳动物物种中广泛保守的假说提供了理论基础。哺乳动物的排卵可分为诱导排卵(即由交配刺激引起)和自发排卵(即由内分泌节律引起)。然而，在诱导排卵器和自发排卵器的两端之间存在着一个系统发育的连续体，并且两者都有一些共同的机制。在一系列开创性的研究中，我们最近证实：1)在骆驼、羊驼(两者都是诱导排卵器)和牛(自发排卵器)的精浆中存在一种相对大分子(&gt；30kD)的蛋白质，能够诱导排卵；2)精浆中的OIF是通过全身而不是局部途径起作用的；3)精浆中的OIF是有效的促黄体生成素释放因子；以及4)OIF诱导的循环中黄体生成素的升高与黄体发育和分泌增强有关。在诱导排卵器和自发排卵器中都发现了OIF，这是一个新的发现，对于科学理解所有物种的生育能力具有广泛的意义。本研究的具体目标是：1)分离、纯化和鉴定OIF的生化组成；2)确定OIF在物种间的保守程度；3)确定OIF在诱导排卵和黄体发生中的作用机制；4)确定OIF的组织来源。精液中的排卵诱导因子的特征将对所有哺乳动物排卵过程的传统概念产生深远的影响，并从根本上挑战这些概念。这项研究的一个重要应用将涉及诊断以前未知的男性和女性因素不孕的原因，并开发改善或预防受孕的替代方法。

Ovulation is a fundamental event in the reproductive process of all mammalian species. Ovulation failure or untimely ovulation has a profound impact on fertility. Exciting data from the applicant's laboratory has now cast new light on factors responsible for eliciting the ovulatory cascade. Results document the existence of a novel ovulation-inducing factor (OIF) in seminal plasma, and provide rationale for the hypothesis that OIF is widely conserved among mammalian species as a mechanism for controlling the timing of ovulation. Ovulation in mammals may be classified as induced (i.e., elicited by copulatory stimuli) or spontaneous (i.e., elicited by an endogenous endocrine rhythm). However, a phylogenic continuum exists between the extremes of induced and spontaneous ovulators, and some mechanisms are common to both. In a series of pioneering studies, we have recently documented: 1) the existence of a protein with a relatively large molecular weight (>30 kD) in the seminal plasma of llamas, alpacas (both induced ovulators), and cattle (a spontaneous ovulator) capable of eliciting ovulation; 2) that OIF in seminal plasma acts via a systemic rather than a local route; 3) that OIF in seminal plasma is a potent stimulator of LH release; and 4) that OIF-induced elevation of circulating LH is associated with enhanced luteal gland development and secretion. The discovery of OIF in representatives of both induced and spontaneous ovulators is novel and has broad implications on scientific understanding of fertility in all species. The specific objectives of the proposed study are to 1) isolate, purify and characterize the biochemical composition of OIF, 2) determine the extent to which OIF is conserved among species, 3) determine the mechanism of action of OIF in eliciting ovulation and luteogenesis, and 4) determine the tissue source of OIF. Characterization of an ovulation-inducing factor in semen will have a profound impact on, and fundamentally challenge, traditional concepts of the ovulatory process in all mammals. An important application of this research will involve the diagnosis of previously unknown causes of male- and female-factor infertility, and the development of alternative ways of improving or preventing conception.